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Zhovmer AS, Chandler M, Manning A, et al. Programmable DNA-augmented hydrogels for controlled activation of human lymphocytes. Nanomedicine. 2021;37:102442doi: 10.1016/j.nano.2021.102442.
Zhovmer, A. S., Chandler, M., Manning, A., Afonin, K. A., & Tabdanov, E. D. (2021). Programmable DNA-augmented hydrogels for controlled activation of human lymphocytes. Nanomedicine : nanotechnology, biology, and medicine, 37102442. https://doi.org/10.1016/j.nano.2021.102442
Zhovmer, Alexander S, et al. "Programmable DNA-augmented hydrogels for controlled activation of human lymphocytes." Nanomedicine : nanotechnology, biology, and medicine vol. 37 (2021): 102442. doi: https://doi.org/10.1016/j.nano.2021.102442
Zhovmer AS, Chandler M, Manning A, Afonin KA, Tabdanov ED. Programmable DNA-augmented hydrogels for controlled activation of human lymphocytes. Nanomedicine. 2021 Oct;37:102442. doi: 10.1016/j.nano.2021.102442. Epub 2021 Jul 17. PMID: 34284132; PMCID: PMC8530550.
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Nanomedicine. 2021 Oct;37:102442. doi: 10.1016/j.nano.2021.102442. Epub 2021 Jul 17.

Programmable DNA-augmented hydrogels for controlled activation of human lymphocytes.

Nanomedicine : nanotechnology, biology, and medicine

Alexander S Zhovmer, Morgan Chandler, Alexis Manning, Kirill A Afonin, Erdem D Tabdanov

Affiliations

  1. Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA. Electronic address: [email protected].
  2. Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, USA.
  3. Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
  4. Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, USA. Electronic address: [email protected].
  5. Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA. Electronic address: [email protected].

PMID: 34284132 PMCID: PMC8530550 DOI: 10.1016/j.nano.2021.102442

Abstract

Contractile forces within the planar interface between T cell and antigen-presenting surface mechanically stimulate T cell receptors (TCR) in the mature immune synapses. However, the origin of mechanical stimulation during the initial, i.e., presynaptic, microvilli-based TCR activation in the course of immune surveillance remains unknown and new tools to help address this problem are needed. In this work, we develop nucleic acid nanoassembly (NAN)-based technology for functionalization of hydrogels using isothermal toehold-mediated reassociation of RNA/DNA heteroduplexes. Resulting platform allows for regulation with NAN linkers of 3D force momentum along the TCR mechanical axis, whereas hydrogels contribute to modulation of 2D shear modulus. By utilizing different lengths of NAN linkers conjugated to polyacrylamide gels of different shear moduli, we demonstrate an efficient capture of human T lymphocytes and tunable activation of TCR, as confirmed by T-cell spreading and pY foci.

Copyright © 2021 Elsevier Inc. All rights reserved.

Keywords: Mechanobiology; T cell; TCR mechanosensing

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